The primary objective of the proposed research is to analyze the genetic control mechanisms involved in the expression of the 2 enzyme systems primarily responsible for alcohol metabolism in humans, namely alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Specifically we will analyze the following: a) the number and human chromosomal location of structural genes coding for ADH and ALDH; b) factors involved in the regulation of expression of these enzymes at the cellular level and in the case of ADH, at the gene level. To accomplish these objectives we will continue to develop and analyze somatic cell hybrids and cybrids which can be used for analysis of these differentiated enzymes. In addition, we will continue to develop and characterize monospecific and monoclonal antibodies to human ADH. We will develop cDNA probes for ADH genes. These cDNA probes will be used to confirm the human ADH gene assignments, and to further regionally assign these genes. In addition, the cDNA probes will be used to investigate the tissue specific and developmental regulation of ADH. For this purpose, ADH expressing and non-expressing tissues, and tissues which express a single form of ADH, will be used to quantitate and characterize translatable mRNA which hybridizes to the cDNA probes.